A large portion of the U.S. population is exposed simultaneously to chemical carcinogens and to various inhaled respiratory toxins. Although inhaled toxins like ozone are known to damage pulmonary cell populations such as Clara cells which contain cytochrome P-450 mixed function oxygenase activity and to markedly alter levels of potential carcinogen detoxifying nucleophiles such as glutathione, no thorough investigations have been reported on whether exposure to pollutant gases affects the pathways for metabolic activation or detoxification of chemical carcinogens and toxins in the lung. Thus, the proposed research is designed to examine the effects of ozone and nitrogen dioxide exposure on the activities of three enzyme systems responsible for the formation and detoxification of chemically reactive metabolites in the lung. Dose response, time course, dose x time and intermittent exposure studies will be done in the rat to define the relationships between exposure and enzymatic activity. Also, rats will be exposed to ozone or NO2 and sacrificed at time periods after exposure when pulmonary cell populations such as Clara cells and Type II cells have been shown to proliferate. Enzymatic activities to be monitored include: epoxide hydrase, glutathione S-transferases and cytochrome P-450 mixed function oxygenases. The complete profile of metabolites from benzo(a)pyrene in lung microsomes from pollutant and air exposed animals will be monitored by high pressure liquid chromatography. Activities will be measured in untreated and animals 3-methylcholanthrene pretreated before exposure. This investigation will help clarify how ozone and nitrogen dioxide exposure affects the balance between metabolic activation and detoxification of chemical toxins and carcinogens in the lung.